Many transgender individuals want to have children and are pursuing reproductive care. Limited research has described the experiences of transgender individuals during pregnancy, and no known studies ...have examined reproductive genetic counseling sessions with this patient population. To understand what topics and considerations are explored within this sector of reproductive care, prenatal and preconception genetic counselors that have seen a transgender patient and/or transgender partner of a patient were recruited through an email blast to members of the National Society of Genetic Counselors. Nine genetic counselors completed phone interviews. Content analysis was used to identify, quantify, and examine the concepts within the transcripts. Six major themes emerged: (1) Trans individuals were referred for common genetic counseling indications, (2) genetic counselors were driven to think of more inclusive language, (3) genetic counselors considered ways to make written materials more inclusive, (4) trans individuals expressed discomforts in the prenatal/preconception setting, (5) genetic counselors observed challenges with the care team, and (6) genetic counselors felt underprepared. This study identifies areas within reproductive spaces of genetic counseling that could be more inclusive, particularly relating to commonly used gendered language and written materials, and provides training recommendations for genetic counselors. Additionally, we outline the reported areas of discrimination for these patients and partners, and discuss ways that genetic counselors can be advocates for respectful and equitable care within their clinics.
Intersex people have variations in their sex characteristics that do not exclusively fall within binary definitions of male and female. This community experiences discrimination in the medical ...setting due to the pathologization of intersex bodies, including ‘normalizing’ genital surgeries without the child's consent. While research has explored biomedical aspects contributing to intersex variations, there is limited research centering intersex people's perspectives on their healthcare experiences. The aim of this qualitative study was to understand the experiences of intersex people in the medical setting, with the goal of providing recommendations to clinicians to promote affirming healthcare practices. Between November 2021 and March 2022 we conducted 15 virtual semi-structured interviews with members of the intersex community about their experiences with healthcare providers and perspectives on how their care could be improved. Participants were recruited through social media, with the majority residing in the United States. Through reflexive thematic analysis, 4 major themes were conceptualized: (1) the exclusion of intersex people in binary frameworks, (2) the common experience of medical trauma, (3) the value of psychosocial support, and (4) systemic change to address intersex healthcare. Recommendations were generated based on participants' narratives, including a recommendation for providers to use a trauma-informed approach to care. Healthcare providers must prioritize patient autonomy and ensure consent throughout their medical visits in order to promote intersex affirming care. Depathologization of intersex variations and comprehensive teachings of intersex history and medical care must be incorporated into medical curricula to mitigate experiences of medical trauma and to relieve the burden placed on patients to be their own medical experts and advocates. Participants shared the value of being connected to support groups and mental health resources. Systemic change is needed for the normalization and demedicalization of intersex variations and for the medical empowerment of the intersex community.
•Intersex people are excluded in binary frameworks of sex and gender.•Pathologizing language in clinical settings harms intersex patients.•Autonomy should be at the forefront of intersex healthcare.•Healthcare providers must be more thoroughly educated on intersex variations.•Trauma-informed, patient-centered approaches are key when caring for intersex people.
The histone H2A variant H2A.Z is essential for embryonic development and for proper control of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions of amino acid ...sequence of H2A.Z likely determine its functional specialization compared to core histone H2A. For example, H2A.Z contains three divergent residues in the essential C-terminal acidic patch that reside on the surface of the histone octamer as an uninterrupted acidic patch domain; however, we know little about how these residues contribute to chromatin structure and function. Here, we show that the divergent amino acids Gly92, Asp97, and Ser98 in the H2A.Z C-terminal acidic patch (H2A.Z(AP3)) are critical for lineage commitment during ESC differentiation. H2A.Z is enriched at most H3K4me3 promoters in ESCs including poised, bivalent promoters that harbor both activating and repressive marks, H3K4me3 and H3K27me3 respectively. We found that while H2A.Z(AP3) interacted with its deposition complex and displayed a highly similar distribution pattern compared to wild-type H2A.Z, its enrichment levels were reduced at target promoters. Further analysis revealed that H2A.Z(AP3) was less tightly associated with chromatin, suggesting that the mutant is more dynamic. Notably, bivalent genes in H2A.Z(AP3) ESCs displayed significant changes in expression compared to active genes. Moreover, bivalent genes in H2A.Z(AP3) ESCs gained H3.3, a variant associated with higher nucleosome turnover, compared to wild-type H2A.Z. We next performed single cell imaging to measure H2A.Z dynamics. We found that H2A.Z(AP3) displayed higher mobility in chromatin compared to wild-type H2A.Z by fluorescent recovery after photobleaching (FRAP). Moreover, ESCs treated with the transcriptional inhibitor flavopiridol resulted in a decrease in the H2A.Z(AP3) mobile fraction and an increase in its occupancy at target genes indicating that the mutant can be properly incorporated into chromatin. Collectively, our work suggests that the divergent residues in the H2A.Z acidic patch comprise a unique domain that couples control of chromatin dynamics to the regulation of developmental gene expression patterns during lineage commitment.
Recruitment obstacles with Spanish‐speaking individuals and members of marginalized communities have been documented in the literature in narrative form, but quantitative data on effective strategies ...are limited. Within our research protocol assessing the impact of a storytelling intervention on knowledge and uptake of cell‐free DNA (cfDNA) aneuploidy screening, three different recruitment strategies were trialed and enrollment rates were compared. Throughout the study, field notes were collected from observations in recruitment efforts. We demonstrate the effectiveness of language‐concordant, personal interactions, and culturally tailored materials for recruitment of Spanish‐speaking participants into genomic research studies. We also offer commentary on the experience of the researchers that provides insights to inform recruitment methods for marginalized communities.
Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a ...heart-associated lncRNA in mouse. Using multiple embryonic stem cell (ESC) differentiation strategies, we show that Bvht is required for progression of nascent mesoderm toward a cardiac fate. We find that Bvht is necessary for activation of a core cardiovascular gene network and functions upstream of mesoderm posterior 1 (MesP1), a master regulator of a common multipotent cardiovascular progenitor. We also show that Bvht interacts with SUZ12, a component of polycomb-repressive complex 2 (PRC2), during cardiomyocyte differentiation, suggesting that Bvht mediates epigenetic regulation of cardiac commitment. Finally, we demonstrate a role for Bvht in maintaining cardiac fate in neonatal cardiomyocytes. Together, our work provides evidence for a long noncoding RNA with critical roles in the establishment of the cardiovascular lineage during mammalian development.
Display omitted
► Braveheart (Bvht) is a heart-associated long noncoding RNA in the mouse ► In embryonic stem cells, Bvht is necessary for cardiovascular lineage commitment ► Bvht functions upstream of MesP1 to regulate a core cardiac gene network ► Bvht interacts with PRC2 to mediate epigenetic activation of the cardiac program
Braveheart (Bvht) is a heart-associated long noncoding RNA that is necessary for cardiovascular lineage commitment in embryonic stem cells. Its interaction with the polycomb complex suggests that it may regulate the cardiac program epigenetically.
The histone H2A variant H2A.Z is essential for embryonic development and for proper control of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions of amino acid ...sequence of H2A.Z likely determine its functional specialization compared to core histone H2A. For example, H2A.Z contains three divergent residues in the essential C-terminal acidic patch that reside on the surface of the histone octamer as an uninterrupted acidic patch domain; however, we know little about how these residues contribute to chromatin structure and function. Here, we show that the divergent amino acids Gly92, Asp97, and Ser98 in the H2A.Z C-terminal acidic patch (H2A.ZAP3) are critical for lineage commitment during ESC differentiation. H2A.Z is enriched at most H3K4me3 promoters in ESCs including poised, bivalent promoters that harbor both activating and repressive marks, H3K4me3 and H3K27me3 respectively. We found that while H2A.ZAP3 interacted with its deposition complex and displayed a highly similar distribution pattern compared to wild-type H2A.Z, its enrichment levels were reduced at target promoters. Further analysis revealed that H2A.ZAP3 was less tightly associated with chromatin, suggesting that the mutant is more dynamic. Notably, bivalent genes in H2A.ZAP3 ESCs displayed significant changes in expression compared to active genes. Moreover, bivalent genes in H2A.ZAP3 ESCs gained H3.3, a variant associated with higher nucleosome turnover, compared to wild-type H2A.Z. We next performed single cell imaging to measure H2A.Z dynamics. We found that H2A.ZAP3 displayed higher mobility in chromatin compared to wild-type H2A.Z by fluorescent recovery after photobleaching (FRAP). Moreover, ESCs treated with the transcriptional inhibitor flavopiridol resulted in a decrease in the H2A.ZAP3 mobile fraction and an increase in its occupancy at target genes indicating that the mutant can be properly incorporated into chromatin. Collectively, our work suggests that the divergent residues in the H2A.Z acidic patch comprise a unique domain that couples control of chromatin dynamics to the regulation of developmental gene expression patterns during lineage commitment.
Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified
Braveheart
(
Bvht
), a ...heart-associated lncRNA in mouse. Using multiple embryonic stem cell (ESC) differentiation strategies, we show that
Bvht
is required for progression of nascent mesoderm towards a cardiac fate. We find that
Bvht
is necessary for activation of a core cardiovascular gene network and functions upstream of
MesP1
(mesoderm posterior 1), a master regulator of a common multipotent cardiovascular progenitor. We also show that
Bvht
interacts with SUZ12, a component of Polycomb Repressive Complex 2 (PRC2), during cardiomyocyte differentiation suggesting that
Bvht
mediates epigenetic regulation of cardiac commitment. Finally, we demonstrate a role for
Bvht
in maintaining cardiac fate in neonatal cardiomyocytes. Together, our work provides evidence for a long noncoding RNA with critical roles in the establishment of the cardiovascular lineage during mammalian development.
PDF
